Effect of Ipomoeassin F on the Synthesis of Membrane and Secretory Proteins in Triple-Negative Breast Cancer Cells

Ipomoeassin F (Ipom-F) is a natural compound that exhibits a potent cytotoxic effect on triple-negative breast cancer (TNBC) cells. The mechanism underlying this selective potency remains unclear. To elucidate this mechanism, we analyzed the proteome profiles of the TNBC MDA-MB-231 cells after exposure to Ipom-F at different time points and increasing doses using a quantitative proteomic method. Our proteomic data demonstrate that the major effect of Ipom-F on MDA-MB-231 cells is the inhibition of membrane and secreted protein expression. These findings align with the recently uncovered molecular mechanism of action of Ipom-F, which binds to Sec61-α and inhibits the cotranslational import of proteins into the endoplasmic reticulum. We have defined a subset of membrane and secreted proteins particularly sensitive to Ipom-F. Analysis of the expression of these Ipom-F-sensitive proteins in cancer cell lines and breast cancer tissues reveals that some of these proteins are upregulated in TNBC cells. This suggests that TNBC cells may have adapted to the elevated levels of these proteins, making them more dependent on their expression. Consequently, inhibiting these proteins leads to a crisis in proliferation and/or survival. Additionally, our data suggests that Ipom-F may act as an immunosuppressive agent.